Carbohydrate Antigens - ACS Publications - American Chemical Society

Chapter 1 Michael Heidelberger April 29, 1888—June 25, 1991

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Elvin A. Kabat Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032

Michael Heidelberger was a Leonardo da Vinci Renaissance Man (1-4). Trained in Organic Chemistry, he became the father of Quantitative Immunochemistry . He brought the precise methods of analytical chemistry to the determination of antibodies, antigens and complement on a weight basis, providing the "gold meter bar" against which the more sensitive and rapid but less precise methods of modern immunology and molecular biology such as radioimmunoassay and ELISA could be standardized and compared. He designed the f i r s t refrigerated centrifuge in desperation because his technician kept getting colds from working in the cold room. Following his design, International Equipment Co. wound a brine cooling c o i l around a size 2 centrifuge. Soon everyone had them. He received f i f t y dollars for writing the manual. He never gave up working with his own hands and was in the laboratory a few weeks before his death. His incisive mind retained i t s sharpness during his entire l i f e . 1

Apart from his science, Michael loved music and was an accomplished, professional level c l a r i n e t i s t . He wrote a Wedding March which was played at his two marriages. He was always playing chamber music with friends and v i s i t i n g s c i e n t i s t s . He had a keen interest in social and p o l i t i c a l issues as well. Michael was a gifted lecturer and a great teacher, especially at the laboratory bench. He was known for his generosity, kindness and fairness, especially in giving credit to younger people. He was always accessible; the door of his laboratory was open for anyone to drop in and chat or ask his advice. The term Immunochemistry had been introduced e a r l i e r by Svante Arrhenius i n 1907 as t h e t i t l e t o a book o f lectures. 0097-6156/93/0519-0001$06.00/0 © 1993 American Chemical Society

Garegg and Lindberg; Carbohydrate Antigens ACS Symposium Series; American Chemical Society: Washington, DC, 1993.


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H i s f i r s t two s c i e n t i f i c papers with F.S. Metzger at Columbia appeared i n 1908. He authored over 350 papers, p u b l i s h i n g i n every decade of t h i s century but the 1990's. At the time of h i s death, he l e f t an e x t e n s i v e manuscript "Cross r e a c t i o n s of 56 b a c t e r i a l p o l y s a c c h a r i d e s with 24 antipneumococcal, three a n t i s a l m o n e l l a , one a n t i k l e b s i e l l a and antimycoplasma s e r a " (5) t h a t he had been working on f o r two years and which w i l l be submitted f o r p u b l i c a t i o n . He and Oswald Avery i s o l a t e d and i d e n t i f i e d the types p e c i f i c substances of pneumococci as p o l y s a c c h a r i d e s , opening a v a s t new area of immunology. He founded a school of students and c o l l e a g u e s who explored the immunology and immunochemistry of b a c t e r i a l and other p o l y s a c c h a r i d e s as w e l l as the immunochemistry of p r o t e i n s , a n t i b o d i e s , antigens and complement. He r e c e i v e d a host of awards, 15 honorary degrees and 46 medals i n c l u d i n g the N a t i o n a l Medal of Science from P r e s i d e n t Lyndon B. Johnson i n 1967. I was immensely proud t o have shared the L o u i s a Gross Horwitz P r i z e i n 1977 with Michael and with Henry Kunkel. In 1957 the Michael Heidelberger Lecture was e s t a b l i s h e d at Columbia. Michael attended a l l but the l a s t two and o f t e n l e d i n the q u e s t i o n i n g . Our a s s o c i a t i o n was a f o r t u n a t e s t r o k e of f a t e . My f a t h e r had been having severe f i n a n c i a l d i f f i c u l t i e s and to t r y t o help him my mother began s e l l i n g dresses i n our apartment. Mrs. Nina Heidelberger, Michael's f i r s t wife, whom we d i d not know, heard about t h i s , came i n and bought some dresses. My mother learned t h a t Michael was an A s s o c i a t e P r o f e s s o r of Biochemistry at Columbia, and was doing r e s e a r c h . She t o l d Mrs. Heidelberger about me and about my i n t e r e s t i n Chemistry and i n r e s e a r c h . Mrs. Heidelberger suggested t h a t I speak t o M i c h a e l . I dropped i n at h i s l a b o r a t o r y i n the Department of Medicine a t the C o l l e g e of P h y s i c i a n s and Surgeons s e v e r a l mornings between Sept. and Nov. 1932, t o l d him about some r e s e a r c h I was doing at C i t y C o l l e g e d u r i n g the afternoons and about my d e s i r e f o r a c a r e e r i n Science. He had g e n e r a l l y only taken p o s t d o c t o r a l f e l l o w s , and had never had a graduate student. He had had only a high school graduate who made s o l u t i o n s , helped i n washing glassware, cleaned the desktop, e t c . but Michael s a i d he could not o f f e r such a p o s i t i o n t o a c o l l e g e graduate. I assured him t h a t I would g l a d l y do a l l of these chores, provided t h a t I c o u l d a l s o work t o the top l e v e l of my a b i l i t y , and around Nov. 1932 he s a i d t h a t he would take me on i n h i s l a b o r a t o r y as a l a b o r a t o r y h e l p e r beginning i n Jan. 1933 at a s a l a r y of $90 per month. When I a r r i v e d i t turned out t h a t the P r e s b y t e r i a n H o s p i t a l had announced a 10 or 15 percent pay cut beginning Jan. 1, 1933 and I found my f i r s t paycheck reduced by t h i s amount. Michael t o l d the h o s p i t a l t h a t he had h i r e d me a t 90 d o l l a r s per month beginning i n January and i n s i s t e d t h a t they honor h i s


1. KABAT

Michael Heidelberger: April 29,1888—June 25,1991

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agreement - they d i d . Soon a f t e r I s t a r t e d working with Michael I a p p l i e d t o be a graduate student i n t h e Department o f Biochemistry a t P&S and, a f t e r an i n t e r v i e w and quiz by t h e chairman, Hans T. C l a r k e , was admitted i n Feb. 1933. Thus began my 59 year a s s o c i a t i o n with Michael as h i s f i r s t graduate student and i n 1937 h i s f i r s t Ph.D. Michael and I had s i m i l a r experiences i n many ways he d e s c r i b e d h i m s e l f as o b s t i n a t e and my parents f e l t t h i s way about me. Michael's f a m i l y was i n very modest circumstances and he was always working i n h i s spare time t o make e x t r a money a s s i s t i n g i n summer t e a c h i n g and a b s t r a c t i n g f o r Chemical A b s t r a c t s . My f a t h e r had l o s t h i s business i n 1927 and we were reduced t o desperate circumstances by 1931-32 l i t e r a l l y having no food i n the house. In 193 2 he was making f i v e d o l l a r s a week t o support a family of four. In the summer o f 1931 I worked as an usher i n t h e o l d Loews New York Theater from 1pm t o 3 am seven days a week f o r f i f t e e n d o l l a r s ; t h e j o b gave me s e v e r a l hours o f f i n t h e l a t e afternoon which were perfectly useless. We both wanted t o be chemists and allowed nothing t o stand i n our way. We d i f f e r e d g r e a t l y i n our r e l a t i o n t o music, and our musical a b i l i t i e s , however. In elementary school we had an assembly each F r i d a y morning o f the f i v e hundred o r so students. A f t e r s i n g i n g one song, the p r i n c i p a l announced, "We w i l l s i n g the song over and w i l l the two Kabat boys (a c o u s i n and I) please keep q u i e t . " I a c t u a l l y l i k e d music. My mother played the piano very w e l l . My t a l e n t s were not as broad as Michael's. (For a d d i t i o n a l r e f e r e n c e s and other aspects o f Michael's c a r e e r see 6-14).

REFERENCES

1. P h i l l i p s , Harlan B. 1969. Michael Heidelberger V o l . I An oral history. Four tapes covering the period from Michael's b i r t h i n 1888 through 1968, pp. 1-205. V o l . II Documents and correspondence during t h i s period. National Library of Medicine. A gold mine of documented information. Since I started working with Michael in 1933, I was able to refresh my memory of many events. The rest of Michael's papers has been given to the National Library of Medicine by his grandson, P h i l i p Heidelberger. 2. Heidelberger, Michael. 1984. Reminiscences - A "Pure" Organic Chemist's Downward Path. Immunological Reviews 81:7-19. Reprinted and extended with permission from Ann. Rev. Microbiol. 31:1-12, 1977.


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3. Heidelberger, Michael 1984. Reminiscences - 2. The Years At P. and S. Immunological Reviews 82:7-27. Reprinted with permission from Ann. Rev. Biochem. 1979, 1-21. 4.

Heidelberger, Michael 1985. Reminiscences - 3. Retirement. Immunological Reviews 83:5-22. Reprinted and amplified with permission from The University of Chicago, 1981.

5.

Heidelberger, M. 1991. Cross-reactions of various bacteria in antipneumococcal and other antisera. Unfinished manuscript containing much useful information. Will be in Michael Heidelberger Collection at the National Library of Medicine and w i l l be prepared for publication.

6. Kabat, E.A. 1988. FASEB J. 2:2233.

Michael Heidelberger—Active at 100.

7. Kabat, E.A. 1981. Life in the laboratory. Trends in Biochemical Sciences 6:5. Willstätter and Emil Fischer as seen by Hermann O.L. Fischer, Emil Fischer's son. 8. Kabat, E . A . 1975. Michael Heidelberger as Carbohydrate Chemist. Carbohydrate Research 40:1.

a

9. Kabat, E . A . 1978. Life in the laboratory. Trends in Biochemical Sciences 3:87. 10. L ü d e r i t z , O . , Westphal, O. and Staub, A . - M . 1966. Immunochemistry of O and R Antigens of Salmonella and Related Enterobacteriaceae. Bact. Revs. 30:192-255. 11. Staub, A . - M . 1991. Letter of July 24 to Dr. Stratis Avrameas in response to my request to him to send me information about Michael's a c t i v i t i e s at the Pasteur Institute. 12. Wu, H . , Sah, P.P.T. and Li, C.P. 1928-29. Composition of Antigen-Precipitin P r e c i p i t i n . Proc. Soc. Exp. B i o l . Med. 26:737-738. 13. Kabat, E.A. 1985. Obituary: June 15, 1916 -Sept. 18, 1984.

Manfred Martin Mayer J . Immunol. 134:655.

14. Bendiner, E . L . 1983. Heidelberger at 95, still "pigheadedly productive". Hospital Practice 18:214215, 220-222, 226-227, 230-234. RECEIVED April 9, 1992


Carbohydrate Antigens - ACS Publications - American Chemical Society

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